The overall goals of this project are to elucidate the relationships between local measures of flow, transport capacity, metabolism (particularly energy metabolism), and oxygen consumption in the hearts of animals and humans. The concept is there is local "impedance matching", on the basis that the capacities for each of these elements of the overall process of delivery and utilization of substrates are all likely to be related to the local needs for contractile work or force development. The stimulus for this exploration stems from the observations of the 10-fold range of regional flows in the hearts of normal awake baboons (King et al, 1985) and the apparent matching of local flows and local transport of fatty acids in running dogs (Caldwell et al., 1994). While we cannot yet combine the measurement of local force development with measures of local flow and metabolism, we are planning with Dr. Peter Hunter, Auckland University, to design experiments toward gathering such data. He wil l spend much of the spring of 1996 here in our unit. The work to be accomplished encompasses: (1) A series of studies to characterize heterogeneities in cardiac microvascular form and regional blood flows, using morphometric techniques combined with microsphere-based measures of local flow, using new fractal autocorrelation techniques to determine the directionality of the correlations among local flows, and determining flow heterogeneity at high spatial resolution in large hearts. (2) The development of methods of analysis for interpreting signals from 15O-oxygen, 15O-water, and 15O-carbon monoxide residue functions (by PET imaging) in the heart and the methods for estimating regional oxygen consumption from these hearts and displaying parametric images of such features as local oxygen metabolic rate, vascular volumes, and permeability-surface area products. (3) A series of studies to determine if increased myocardial metabolism reduces the degree of flow heterogeneity in the heart overall in dogs during control states, adrenergic stimu lation and atrial pacing. (4) This research, in collaboration with a parallel series of PET imaging studies performed under the leadership of James H. Caldwell (HL50239) requires service support in radioisotope chemistry, in physics of PET imaging (equipment maintenance and software development) and in imaging procedures, all of which are in collaboration with personnel in Radiology.